BACKGROUND: Stone heart syndrome was first described by Denton Cooley in 1972 and represents an extremely rare but severe complication following cardiac surgery. The condition is characterized by an irreversible, concentric, spastic contracture of the myocardium occurring during reperfusion which does not respond to either pharmacological or mechanical interventions. The underlying pathophysiology remains poorly understood, but an association with suboptimal cardioprotection and prolonged ischemia time has been suggested. CASE PRESENTATION: A 22-year-old otherwise healthy patient was admitted for elective mitral valve surgery due to severe mitral regurgitation caused by bileaflet prolapse and a history of cardiomyopathy of unclear etiology. Upon weaning from cardiopulmonary bypass, the patient developed biventricular heart failure requiring veno-arterial extracorporeal membrane oxygenation. Transesophageal echocardiography showed a stone heart. In the following days, temporary mechanical circulatory support was escalated to veno-arterio-venous extracorporeal membrane oxygenation and Impella. On postoperative day 5, a durable left ventricular assist device was implanted. Due to refractory stone heart syndrome, the patient was evaluated for heart transplantation which was successfully performed on postoperative day 23. The subsequent course was largely uneventful. The patient was discharged to rehabilitation at 6 weeks post transplantation. CONCLUSION: Acute terminal heart failure due to perioperative stone heart is rare. In cases of irreversible global myocardial injury, orthotopic heart transplantation remains the only curative treatment option.